The invention relates to a method and device for monitoring an implant, and in particular to a method and device for correcting luminescent signals emitted from the implant.
The monitoring of the level of analyte, such as glucose, lactate or oxygen, in certain individuals is important to their health. High or low levels of glucose, or other analytes, may have detrimental effects or be indicative of specific health states. The monitoring of glucose is particularly important to individuals with diabetes, a subset of whom must determine when insulin is needed to reduce glucose levels in their bodies or when additional glucose is needed to raise the level of glucose in their bodies.
A conventional technique used by many individuals with diabetes for personally monitoring their blood glucose level includes the periodic drawing of blood, the application of that blood to a test strip, and the determination of the blood glucose level using calorimetric, electrochemical, or photometric detection. This technique does not permit continuous or automatic monitoring of glucose levels in the body, but typically must be performed manually on a periodic basis. Unfortunately, the consistency with which the level of glucose is checked varies widely among individuals. Many people with diabetes find the periodic testing inconvenient, and they sometimes forget to test their glucose level or do not have time for a proper test. In addition, some individuals wish to avoid the pain associated with the test. Unmonitored glucose may result in hyperglycemic or hypoglycemic episodes. An implanted sensor that monitors the individual's analyte levels would enable individuals to monitor their glucose, or other analyte levels, more easily.
A variety of devices have been developed for monitoring of analytes (e.g., glucose) in the blood stream or interstitial fluid of various tissues. A number of these devices use sensors that are inserted into a blood vessel or under the skin of a patient. These implanted sensors are often difficult to read or to monitor optically, because of low levels of florescence in the presence of high scatter due to dynamic changes in skin conditions (e.g., blood level and hydration). The skin is highly scattering, and the scattering may dominate the optical propagation. Scatter is caused by index of refraction changes in the tissue, and the main components of scatter in the skin are due to lipids, collagen, and other biological components. The main absorption is caused by blood, melanin, water, and other components.
One device, disclosed in published US patent application 20090221891 to Yu, includes components of an assay for glucose. An optical signal is read out transcutaneously by external optics when the sensor is implanted in vivo. A fluorimeter separately measures, for a donor chromophore and an acceptor chromophore, an excitation light intensity, an ambient light intensity, and an intensity of combined luminescent and ambient light. Measurements are taken by holding the fluorimeter close to the skin and in alignment with the sensor. The final output provided is the normalized ratio between the luminescent intensity from the two fluorophores, which may be converted to analyte concentration using calibration data. A calibration curve is established empirically by measuring response versus glucose concentration. Although this device provides some light signal correction, it may still be difficult to obtain accurate readings due to dynamic skin changes that cause optical scattering and absorption of light emitted from the implant.
US patent application 20110028806 to Merritt discloses another procedure and system for measuring blood glucose levels. A set of photodiodes detects the luminescence and reflectance of light energy emitted from one or more emitters, such as LEDs, into a patient's skin. Small molecule metabolite reporters (SMMRs) that bind to glucose are introduced to tissue of the stratum corneum and the epidermis to provide more easily detected luminescence. The test results are calibrated with a reflectance intensity measurement taken at approximately the excitation wavelength. In addition, the method includes measuring a second luminescence and reflectance intensity to normalize data from the first set of measurements. First luminescence and reflectance intensity measurements are taken at a site treated with an SMMR. Second luminescence and reflectance intensity measurements are taken at an untreated, background site. The background measurement is then used to correct for the background tissue luminescence and absorption through a wavelength normalization. Although this method provides some light signal correction for background luminescence and reflectance, it may still be difficult to obtain accurate and/or consistent glucose readings from glucose-binding molecules in the epidermis.
There is still a need for a small, compact device that can accurately and consistently monitor an implanted sensor and provide signals to an analyzer without substantially restricting the movements and activities of a patient. Continuous and/or automatic monitoring of the analyte can provide a warning to the patient when the level of the analyte is at or near a threshold level. For example, if glucose is the analyte, then the monitoring device might be configured to warn the patient of current or impending hyperglycemia or hypoglycemia. The patient can then take appropriate actions.